Modulation of luteinizing hormone(LH) release by clonidine and opioid peptides in castrated male rats

The effect of clonidine, a central alpha-adrenergic agonist, on the suppression of LH release induced by beta-endorphin or FK33-824, an endogenous opioid peptide or its synthetic analog, was investigated in castrated male rats, with or without pretreatment with reserpine. Pulsatile LH secretion was inhibited by intravenous injection of FK33-824 (400 micrograms/kg), or intraventricular injection of beta-endorphin (5 micrograms). Without pretreatment with reserpine, intraperitoneal administration of clonidine (1 mg/kg) failed to reverse the inhibition of LH release induced by these peptides. However, with pretreatment with reserpine (10 mg/kg), clonidine abolished the inhibitory effect on LH secretion induced by these peptides in castrated male rats. These data indicate that, unlike the results in ovariectomized, steroid-primed rats, pretreatment with reserpine allows the alpha-adrenergic system to act more peripherally than the opioid neuronal system in a neuronal network-regulating LH release in castrated male rats.     

Delta sleep-inducing peptide (DSIP) stimulates growth hormone (GH) release in the rat by hypothalamic and pituitary actions

To evaluate possible effects of delta sleep-inducing peptide on GH release, the peptide was micro-injected into conscious animals with third ventricular cannulae and blood samples were drawn from indwelling external jugular vein cannulae. Ovariectomized animals were used in order to eliminate gonadal steroid feedback. In the initial experiment, intraventricular injection of 5 micrograms of the peptide induced an elevation of GH which became significant by 30 min and persisted for the 120 min duration of the experiment after the injection. Diluent-injected animals showed a slight initial drop in GH and then no increase. The increase in plasma GH induced by the peptide was dose-related with a minimal effective dose of 0.1 microgram and a linear log-dose increase to a dose of 10 micrograms. This effect is presumably mediated hypothalamically via a dopaminergic mechanism since it could be blocked by pre-treatment of the animals with pimozide, a dopamine receptor blocker. Dispersed overnight, cultured pituitary cells from ovariectomized rats exhibited a dose-related increase in GH release in static incubations with DSIP. A response occurred with the lowest dose tested (10(-12) M) which increased to a maximum at 10(-10) M DSIP. The responses then declined at higher doses such that they were no longer significant at doses of 10(-7) and 10(-5) M. The increase even at the most effective dose was approximately 50% above the basal values. The results are consistent with the hypothesis that DSIP may be involved in GH release via a dopaminergic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of neuropeptide Y, NPY analog (norleucine4-NPY), galanin and neuropeptide K on LH release in ovariectomized (ovx) and ovx estrogen, progesterone-treated rats

We studied the effects on plasma LH levels of intracerebroventricular (ICV) administration of neuropeptide Y (NPY), NPY analog (NPY-A), galanin (GAL) and neuropeptide K (NPK) in ovariectomized (ovx) and in ovx rats pretreated with estradiol benzoate (EB) and progesterone (P). Plasma LH levels were estimated in blood drawn from an intrajugular cannula before (0 min) and at 10, 20, 30 and 60 min after the ICV injection of either saline (3 microliter) or one of the neuropeptides in saline. The three classes of peptides elicited different LH responses in the two experimental paradigms. NPY and NPY-A (0.5 or 2 micrograms) decreased LH release in ovx rats and stimulated LH release in EBP ovx rats. However, GAL (0.5, 2 or 10 micrograms) failed to suppress LH release in ovx rats, but it readily increased plasma LH levels in a dose-related fashion in EBP ovx rats. In contrast, NPK readily decreased LH release in ovx rats in a time-related fashion for up to 60 min, but was mildly effective in EBP ovx rats as only a high dose of 10 micrograms produced a small significant increase. Collectively, our results show that (1) NPY can differentially effect LH release in ovx and EBP ovx rats but this property is not equally shared by the neuropeptides that have a similar anatomical disposition in the hypothalamus and (2) the excitatory effects of GAL are demonstrable in the steroid-primed rats and the inhibitory effects of NPK are apparent in the steroid-unprimed ovx rats. Since NPK induced a long-lasting marked suppression with little evidence of LH excitation at low doses, we speculate that either NPK alone or in conjunction with other peptides may mediate the suppression of LH release induced by gonadal steroids.     

Delta sleep-inducing peptide (DSIP): a still unresolved riddle

Delta sleep-inducing peptide (DSIP) was isolated from rabbit cerebral venous blood by Schoenenberger-Monnier group from Basel in 1977 and initially regarded as a candidate sleep-promoting factor. However, the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although DSIP itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure. DSIP structure is different from any other known representative of the various peptide families. In this mini-review we hypothesize the existence of a DSIP-like peptide(s) that is responsible (at least partly) for DSIP-like immunoreactivity and DSIP biological activity. This assumption is based on: (i) a highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow-wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS-promoting activity of a naturally occurring dermorphin-decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep-suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP-like peptide and its role in neuroendocrine regulation.     

Correlation between LH and estrogen receptor turnover in pituitary and hypothalamus of castrate rats following estrogen agonists and antagonists

A series of studies was undertaken to correlate the short-term dynamics of LH secretion and depletion-replenishment patterns of estrogen receptors (ER) in hypothalamic and pituitary cytosols of ovariectomized rats. Animals castrated for 2 weeks were administered various test compounds and analyzed at 1, 3, 5, 10 and 15 h post-treatment. A single injection of 10 micrograms 17 beta-estradiol (E2) to ovariectomized rats elicited a rapid depletion of ER in both pituitary and hypothalamus and a dramatic, though delayed, fall in serum LH. ER replenishment occurred in both tissues through 15 h and LH recovered in a similar manner. When cycloheximide was administered along with E2, ER replenishment was completely inhibited in both tissues; serum LH fell and failed to recover. Actinomycin D injected with E2 blocked replenishment in pituitary but not hypothalamus; serum LH recovered in parallel with the hypothalamic ER pattern. 17 alpha-E2 elicited only slight changes in ER and LH was suppressed 10-20% through 15 h. CI-628 caused a near total depletion of pituitary ER with no subsequent replenishment, whereas hypothalamic ER content was virtually unaltered; serum LH was suppressed and later recovered. Orchidectomized rats given 5 micrograms E2 demonstrated a less complete ER depletion in hypothalamus, and an earlier replenishment than that seen in pituitary or hypothalamus of similarly treated ovariectomized females. Serum LH rebounded to 157% of control levels at 15 h. The results indicate that the acute feedback suppression of LH by exposure to estrogens correlates with binding to ER and nuclear translocation. Replenishment and/or retention of cytoplasmic ER in hypothalamus appears to be required for full resumption of LH secretion, following acute suppression.     

Intrahypothalamic action of corticotrophin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat

The effects of intravenous or intraventricular injection of synthetic ovine corticotrophin-releasing factor (oCRF) on plasma levels of anterior pituitary hormones were studied in conscious, ovariectomized (OVX) female rats and compared with the actions of the peptide on dispersed anterior pituitary cells from OVX female rats incubated in the presence of CRF. Third ventricular injection of oCRF in freely moving rats caused a significant increase in plasma levels of ACTH in a dose-related manner with a minimal effective dose of less than 0.5 micrograms (0.1 nmol). The effect was observable at 5 min after injection and persisted for the 60 min duration of the experiment. In contrast, growth hormone levels were significantly depressed within 15 min with a minimal effective intraventricular dose of 0.5 micrograms. The suppression persisted for the duration of the experiment but there was no additional effect of the higher dose of 5 micrograms. Plasma LH levels were also lowered by the highest dose of 5 micrograms (1.0 nmol) of oCRF, with the first significant lowering at 30 min. Lower doses had no effect on plasma LH. Plasma TSH levels were not significantly altered. Control injections of the 0.9% NaCl diluent were without effect on the levels of any of the hormones. Intravenous injection of similar doses of oCRF had no effect on plasma levels of GH or LH. The ACTH-releasing action of the oCRF preparation was confirmed by in vitro incubation of the peptide with dispersed anterior pituitary cells for 2 h. A dose-related release of ACTH occurred in doses ranging from 0.1-10 nM, but there were no effects on the release of the other anterior pituitary hormones. The results suggest that oCRF may act within the hypothalamus to suppress the release of GH and to a lesser extent LH. The stimulation of ACTH release following intraventricular CRF is presumably related to its uptake by portal blood vessels with delivery to the pituitary and stimulation of the corticotrophs.     

Characterization of Delta-Sleep-Inducing Peptide-Evoked Release of Met-Enkephalin from Brain Synaptosomes in Rats

Delta-sleep-inducing peptide (DSIP) stimulates the release of Met-enkephalin (Met-ENK) from superfused slices of the rodent lower brainstem in vitro. In our present study, DSIP (10(-10)-10(-9) M) induced a significant release of Met-ENK from medullary synaptosomes of rats. This DSIP-evoked release of Met-ENK was Ca2+ dependent and tetrodotoxin (TTX) insensitive. Furthermore, DSIP (10(-11)-10(-9) M) significantly increased 45Ca2+ uptake in medullary synaptosomes. These results demonstrate that DSIP acts directly on the nerve endings of Met-ENK-containing neurons to release this pentapeptide by generating a Ca2+ influx into these neurons. Effects of DSIP on Met-ENK release in other discrete brain regions were also studied. Significant DSIP-evoked Met-ENK release from synaptosomes was observed in the cortex, hypothalamus, and midbrain (at concentrations of 10(-10) and 10(-9) M) and in the hippocampus and thalamus (only at 10(-9) M), but not in the striatum. In the hypothalamus, the release of Leu-enkephalin from its synaptosomes was slightly, but not significantly, enhanced by DSIP (10(-10)-10(-8) M). Our findings demonstrate that DSIP triggered a Ca2+ influx in nerve endings to induce a subsequent release of Met-ENK from neurons in only certain brain regions.     

The hypnogenic effects of delta sleep-inducing peptide (DSIP) analogs: a comparative study in rabbits and rats]

Hypnogenic effects of 3 DSIP analogs with a higher stability against aminopeptidase activity have been studied in rabbits and rats using intraventricular administration (injections and infusions). An analog (D-Ala-2) DSIP augmented slow wave and paradoxical sleep within the 5th, 8th and 11th hours of the recording period. An analog (D-Val-2) DSIP made the same within the 8th and 10th hours, and hexapeptide (D-Ala-2) DSIP (1-6) increased sleep during the 1st, 3rd, and 5th hours. Both nonapeptides augmented sleep in rabbits as well as in rats, though hexapeptide produced this effect in rabbits only, that might be related to some difference in distribution and colocalization of endogenous DSIP-like peptide in the pituitary of two rodent species. It may be suggested that hypnogenic activity of DSIP analogs is determined by the structure of administrated molecule, being mediated by such hormones as GRF and CLIP.     

Norepinephrine-like effects of neuropeptide Y on LH release in the rat

Neuropeptide Y, a recently isolated neuropeptide exhibited norepinephrine-like effects on LH release after intracerebroventricular administration at doses from 0.5 to 10 micrograms. While it promptly suppressed LH release in ovariectomized rats, there was a dose-related stimulation of LH secretion in ovarian steroid primed-ovariectomized rats. In view of the evidence that neuropeptide Y may coexist with adrenergic neurotransmitters, these findings suggest that it may play a role in regulation of LH release in the rat, either independently or in concert with catecholamines.     

Effect of acute immunoneutralization of endogenous leptin on prolactin and LH secretion during the afternoon of pro-oestrus or in steroid-treated ovariectomized female rats

Recent data indicate that leptin is involved in the control of reproductive function. Experiments were carried out to analyse the role of endogenous leptin in the regulation of LH and prolactin secretion during the afternoon of pro-oestrus and that induced by ovarian steroids in ovariectomized rats. In the first experiment, cyclic female rats were implanted with intra-auricular and intracerebroventricular (i.c.v.) cannulae and, at pro-oestrus, were injected (i.c.v.) with 10 microliters normal rabbit serum or leptin antiserum (at 13:00 and 14:00 h). Blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the second experiment, female rats in pro-oestrus were injected with normal rabbit serum or leptin antiserum at 16:00 and 18:00 h and blood samples were taken every 10 min between 18:00 and 20:00 h. In the third experiment, adult female rats that had been ovariectomized 2 weeks before were implanted with intra-auricular and i.c.v. cannulae and treated with oestradiol benzoate (30 micrograms s.c.) at 10:00 h and progesterone (2 mg s.c.) 48 h later. Normal rabbit serum (10 microliters) or leptin antiserum (10 microliters) were injected (i.c.v.) at 13:00 and 14:00 h, and blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. In the fourth experiment, hemipituitaries from ovariectomized steroid-treated female rats were incubated in the presence of leptin116-130 (an active fragment of the native molecule), GnRH or leptin + GnRH. Prolactin and LH secretion during the afternoon of pro-oestrus in females treated with leptin antiserum was similar to that observed in animals injected with normal rabbit serum. In ovariectomized female rats, the steroid-induced LH surge increased slightly after administration of leptin antiserum, whereas the prolactin surge remained unchanged. In vitro, leptin116-130 (10(-5) to 10(-8) mol l-1) inhibited LH secretion and modulated the effect of GnRH on LH release, depending on the concentration of GnRH: leptin116-130 (10(-6) mol l-1) reduced the effectiveness of 10(-7) mol GnRH l-1 and increased that of 10(-9) mol GnRH l-1. In conclusion, these experiments indicate that acute immunoneutralization of endogenous leptin does not interfere with spontaneous or steroid-induced LH and prolactin surges. In addition, the finding that leptin116-130 inhibited LH release and modulated the effectiveness of GnRH in vitro provides evidence of the direct modulatory role of leptin on LH secretion acting at the pituitary.     

Effect of beta-adrenergic drugs on LH, FSH, and growth hormone (GH) secretion in conscious, ovariectomized rats

The effects of third ventricular (3V) injection of the beta-adrenergic antagonist, propranolol (PROPR), a selective beta 1-antagonist, metoprolol (MET), a selective beta 2-antagonist, IPS 339, and a beta-adrenergic agonist (-) isoproterenol (ISOPR), on plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), and growth hormone (GH) were studied in conscious, ovariectomized (OVX) rats. Samples were removed from unrestrained rats which had been previously implanted with atrial and 3V cannulae, and plasma hormone levels were determined by radioimmunoassay (RIA). Intraventricular injection of PROPR (30 micrograms), MET (40 micrograms), or IPS 339 (20 micrograms) induced a gradual elevation in plasma GH concentrations, whereas ISOPR (30 micrograms) reduced plasma GH. ISOPR (30 micrograms) brought about a decrease in plasma LH concentrations, but PROPR, MET and IPS 339 had no effect on LH levels. PROPR (30 micrograms) increased plasma FSH concentrations, but there was no significant effect of MET, IPS 339 or ISOPR on FSH secretion. The results indicate that the beta-adrenergic system can inhibit the release of GH, LH, and FSH. This system appears to have a tonic inhibitory effect on GH and FSH but not LH release in the OVX rat.     

Differential changes in the mechanisms controlling luteinizing hormone and prolactin secretion in middle-aged female rats

Serum luteinizing hormone (LH) and prolactin (PRL) concentrations were measured in young (3-4 month old) and middle-aged (10-12 month old) intact female rats on proestrus, in ovariectomized rats after two estrogen injections (estradiol benzoate; EB, 10 micrograms/100 g body weight, s.c.) or after preoptic stimulation in EB-primed ovariectomized rats. Only animals showing regular 4-day estrous cycles were selected for the experiment. The magnitude of proestrous LH surge was significantly smaller in middle-aged than in young rats. Two BE injections, at noon on Days 0 and 3, in ovariectomized middle-aged rats failed to induce surges in LH secretion on Day 4 whereas the same treatment produced LH surges in ovariectomized young rats. The preoptic electrochemical stimulation (50 microA for 60 sec) produced a prompt rise in serum LH levels in ovariectomized EB-primed young but not in middle aged rats. The preoptic stimulation with a larger current (200 microA) induced LH secretin in middle-aged rats. In none of these situations serum PRL concentrations were different between young and middle-age rats. These results suggest differential aging rates in the preoptic mechanisms governing LH and PRL secretion in the rat. The function of the preoptic ovulatory center in responding to the estrogen positive feedback action and inducing LH secretion may become impaired and independent of the PRL control mechanism, even before the regular estrous cycle terminates.     

Effects of arginine vasotocin on levels of plasma gonadotropins and prolactin in ovariectomized conscious rats

Arginine vasotocin was injected into the third ventricle or intravenously in conscious, ovariectomized rats and its effect on gonadotropin and prolactin release evaluated. The peptide lowered plasma levels of both LH and prolactin in doses of 40 or 100 ng given intraventricularly. The higher dose was slightly more effective than the lower dose. Intravenous injection of a 1-microgram dose of vasotocin failed to alter plasma LH in the ovariectomized animals; however, a 5-micrograms dose induced a slight depression apparent at only 60 min following injection. Intravenous injection of 1 microgram produced a significant lowering of plasma prolactin, whereas a dramatic lowering followed the injection of the higher dose. Plasma FSH was unaffected in these experiments. Incubation of dispersed anterior pituitary cells from ovariectomized rats with various doses of vasotocin revealed no effect of the peptide on the release of FSH, LH, or prolactin. It also did not alter the response to LHRH, but it partially blocked the action of dopamine to inhibit prolactin release. The data indicate that quite low doses of arginine vasotocin act within the brain to inhibit LH and prolactin secretion in ovariectomized, conscious animals.     

Improved model for the induction of proestrus-like gonadotropin surges in long-term ovariectomized rats

In long-term (greater than 4 wk) ovariectomized rats the positive response of the gonadotropin release apparatus to a priming dose of estradiol is moderate as compared with that of proestrous rats exposed to endogenous estradiol. In the present study, high sensitivity to estrogen was restored in long-term ovariectomized rats by pretreatment with estradiol benzoate (EB, 20 micrograms, day 0) and progesterone (P, 2.5 mg, day 3). Estradiol benzoate (20 micrograms) given on day 5 induced proestrus-like surges of LH and FSH in the afternoon on day 6. Additional administration of P (2.5 mg at noon on day 6) had a facilitatory effect. Stimulation of LH release could be evoked in rats by the described regimen 1, 6 or 50 wk after ovariectomy. The long-term ovariectomized rat injected with EB and P as described might provide a useful model for neuroendocrinological investigations on the gonadotropin surge mechanism.     

Influence of intracerebroventricular (ICV) injection of ACTH (1-24) on plasma gonadotropin in female rats: dose-response study

The intracerebroventricular (ICV) injection of ACTH (1-24) (0.1, 1.0 and 2.5 micrograms) to adult conscious ovariectomized (OVX) rats caused a dose-related inhibition of plasma LH at 10 min postinjection. The ICV injection of ACTH (1-24) (2.5 micrograms) to OVX rats in the absence or presence of a single dose of estradiol benzoate (OVX + EB): a) Decreased significantly plasma LH levels in OVX rats at 10 and 30 min postinjection. b) Decreased significantly plasma LH levels in (OVX + EB) rats at 10 min but not at 30 min postinjection. c) Did not change plasma FSH levels at 10 or 30 min postinjection in both (OVX) or (OVX + EB) rats. d) Did not change plasma ACTH levels at 10 or 30 min postinjection in (OVX) rats. Our observation suggest that ACTH (1-24) inhibited plasma LH, possibly through brain sites of action.     

Comparison of the effects of neuropeptide Y and adrenergic transmitters on LH release and food intake in male rats

In view of the recent demonstrations that Neuropeptide Y (NPY) and adrenergic transmitters coexist in neurons of the rat brain, we have compared the effects of intraventricular (Ivt) injections of NPY and catecholamines on LH release and food intake in intact male rats. Of the three catecholamines, dopamine (DA), norepinephrine (NE) and epinephrine (E), only E (5.3 micrograms or 15.9 micrograms/rat) significantly stimulated LH release, although NE and E (5.3 micrograms/rat) were equally effective in eliciting food intake in satiated rats. Ivt administration of 10 micrograms NPY significantly stimulated LH release, whereas either lower (0.5 or 2 micrograms/rat) or higher (25 micrograms/rat) doses were ineffective. In contrast, NPY at doses of 0.5 - 10 micrograms/rat increased cumulative food intake in a dose-related fashion. These findings present preliminary evidence of the physiological correlates of the neuronal coexistence of adrenergic transmitters and NPY in the brain and raise the possibility that NPY may normally act either independently, in concert with or via adrenergic systems to evoke LH release and feeding responses in the rat.     

Delta-sleep-inducing peptide (DSIP) inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro

Delta-sleep-inducing peptide (DSIP, 10(-9) - 10(-7) M) significantly inhibited the CRF-induced ACTH release from rat anterior pituitary quarters in vitro. 10(-8) M DSIP showed the most prominent inhibition. DSIP (10(-8) M) also inhibited the CRF-activated cAMP levels in anterior pituitary tissue. DSIP did not influence basal ACTH or cAMP levels. Prostaglandin E2 (PGE2)-release from anterior pituitary quarters was not changed by DSIP. From these results, we conclude that DSIP inhibits CRF-induced ACTH release at the pituitary level through the inhibition of the cAMP system in corticotrophs. The involvement of PGE2 in this phenomenon is unlikely.     

Anticataleptic effect of delta sleep-inducing peptide and its action on brain monoamine oxidase in rats genetically predisposed to catalepsy

Rats with genetic susceptibility to catalepsy (GC strain) were compared with Wistar rats (W). After an intraperitoneal administration of 120 micrograms/100 g delta sleep-inducing peptide (DSIP) in GC rats the duration of cataleptic freezing was shortened (13.8 +/- 9.5 sec against 27.2 +/- 7.5 sec in control). MAO-B activity decreased due to DSIP administration both in GC and W rats. It is hypothesized that the DSIP effect MAO-B in GC rats may correct the lost MAO-A function in deamination of dopamine, a common MAO-A and MAO-B substrate, and the dopaminergic neurotransmission in catalepsy.     

Role of arginine vasopressin in control of ACTH and LH release during stress

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.     

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)